chr15-67132695-C-T

Position:

• chr15-67132695-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_005902.4(SMAD3):​c.207-32200C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.225 in 152,032 control chromosomes in the GnomAD database, including 4,138 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as confers sensitivity (★).

• Frequency: Genomes: 𝑓 0.23 (4138 hom., cov: 32)
• Consequence: SMAD3 NM_005902.4 intron
• Clinical Significance: confers sensitivity criteria provided, single submitter O:1
• Conservation: PhyloP100: -0.995

Genes affected

SMAD3 (HGNC:6769): (SMAD family member 3) The SMAD family of proteins are a group of intracellular signal transducer proteins similar to the gene products of the Drosophila gene 'mothers against decapentaplegic' (Mad) and the C. elegans gene Sma. The SMAD3 protein functions in the transforming growth factor-beta signaling pathway, and transmits signals from the cell surface to the nucleus, regulating gene activity and cell proliferation. This protein forms a complex with other SMAD proteins and binds DNA, functioning both as a transcription factor and tumor suppressor. Mutations in this gene are associated with aneurysms-osteoarthritis syndrome and Loeys-Dietz Syndrome 3. [provided by RefSeq, May 2022]

SMAD3 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.334 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SMAD3	NM_005902.4	c.207-32200C>T		intron_variant		ENST00000327367.9	NP_005893.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SMAD3	ENST00000327367.9	c.207-32200C>T		intron_variant		1	NM_005902.4	ENSP00000332973.4

Frequencies

GnomAD3 genomes AF: 0.225 AC: 34224 AN: 151914 Hom.: 4130 Cov.: 32

Gnomad AFR AF: 0.299

Gnomad AMI AF: 0.158

Gnomad AMR AF: 0.235

Gnomad ASJ AF: 0.266

Gnomad EAS AF: 0.347

Gnomad SAS AF: 0.270

Gnomad FIN AF: 0.136

Gnomad MID AF: 0.244

Gnomad NFE AF: 0.178

Gnomad OTH AF: 0.244

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.225 AC: 34259 AN: 152032 Hom.: 4138 Cov.: 32 AF XY: 0.225 AC XY: 16753 AN XY: 74324

Gnomad4 AFR AF: 0.299

Gnomad4 AMR AF: 0.236

Gnomad4 ASJ AF: 0.266

Gnomad4 EAS AF: 0.347

Gnomad4 SAS AF: 0.270

Gnomad4 FIN AF: 0.136

Gnomad4 NFE AF: 0.178

Gnomad4 OTH AF: 0.241

Alfa AF: 0.189 Hom.: 6038

Bravo AF: 0.237

Asia WGS AF: 0.315 AC: 1094 AN: 3478

ClinVar

Significance: confers sensitivity

Submissions summary: Other:1

Revision: criteria provided, single submitter

Submissions by phenotype

Lung cancer Other:1

confers sensitivity, criteria provided, single submitter

research

Kong Lab, Department of Radiation Oncology, Case Western Reserve University School of Medicine

May 01, 2012

Improve the prediction accuracy for overal survival in non-small cell lung cancer patients -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.61
DANN	Benign	0.27

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs12102171; hg19: chr15-67425033;